Erythropoietin effect on sensorimotor recovery after contusive spinal cord injury: An electrophysiological study in rats

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. It has been shown in rats that the acute administration of recombinant human erythropoietin (rhEPO) following a contusive SCI improves the recovery of hindlimb motor function, as measured with the locomotor BBB (Basso, Beattie, Bresnahan) scale. This scale evaluates overall locomotor activity, without testing whether the rhEPO-induced motor recovery is due to a parallel recovery of sensory and/or motor pathways. Aim of the present study was to utilize an electrophysiological test to evaluate, in a rat model of contusive SCI, the transmission of both ascending and descending pathways across the damaged cord at 2, 5, 7, 11, and 30 days after lesion, in animals treated with rhEPO (n = 25) vs saline solution (n = 25). Motor potentials evoked by epicortical stimulation were recorded in the spinal cord, and sensory-evoked potentials evoked by spinal stimulation were recorded at the cortical level. In the same animals BBB score and immunocytochemical evaluation of the spinal segments caudal to the lesion were performed. In rhEPO-treated animals results show a better general improvement both in sensory and motor transmission through spared spinal pathways, supposedly via the reticulo-spinal system, with respect to saline controls. This improvement is most prominent at relatively early times. Overall these features show a parallel time course to the changes observed in BBB score, suggesting that EPO-mediated spared spinal cord pathways might contribute to the improvement in transmission which, in turn, might be responsible for the recovery of locomotor function.

► Treatment of spinal lesions with rhEPO improves the sensory-motor transmission through the cord. ► The level of myelin in lumbar cord is higher in EPO-treated than in saline-treated rats. ► Changes in motor responses correlate with the higher density of tyrosine hydroxylase-spared fibers. ► Overall neurophysiological improvement parallels the improvement in locomotor behavior. ► We suggest that the improved neural transmission may contribute to locomotor recovery.